A hydrogel is a material consisting of water-filled networks of cross-linked polymers. One of the most important features of this type of material is its hydrophilic nature, which enables many of its varieties to be compatible with the body. Moreover, the physical and chemical properties, which include, but are not limited to, mechanical properties, volume change behavior, drug controlled release behavior, functionalization of chemical moieties, and gel-body interactions, can be well controlled in a hydrogel system. Therefore, a hydrogel is favorable in many kinds of biomedical applications, including, but not limited to, tissue engineering, tissue augmentation, tissue filling, drug delivery, and cell delivery.
However, a hydrogel is a viscoelastic solid, and due to its limited ability to deform, it is difficult to place into the body without surgically opening the body. A special type of hydrogel, sometimes referred to as “in situ” hydrogel, is a material that can change from a viscoelastic liquid to viscoelastic solid (or “sol-gel transition”) when the gel is injected into the body. This property enables the material to be placed in the body by a minimally invasive manner, e.g., by an injection. This additional advantage, together with the other properties stated above, make in situ hydrogels attractive candidates in many biomedical applications. Nevertheless, the development of this type of hydrogel is challenging. One of the most challenging spaces to form an in situ hydrogel is the endoluminal space for endoluminal therapy. “Endoluminal” is an adjective describing a space inside the lumen of a body. A lumen refers to a tube-like structure inside the body. Examples of lumens in the body include, but are not limited to, blood vessels, lymphatic vessels, respiratory tract, digestive tract, fallopian tubes, and ductus deferens. One type of endoluminal therapy is to use an external material to fill up certain spaces inside the lumen. Examples of this type therapy include lumen embolization and ligature. The medical conditions needed for this type of therapy may be of various kinds. One particular example of a medical condition is vascular abnormality.
The prevalence and central role of vascular abnormality in various pathological conditions have been driving the biopharmaceutical industry to develop new medicines and devices. Efficient and secured occlusion of abnormal vessel segments has been one of the major, yet unmet, demands especially in the treatments of arteriovenous malformation (AVM), aneurysm and tumor. Compared with surgery and radiotherapy, endovascular embolization allows minimal invasiveness, less complications and shorter hospitalization. With the recent advancement in intervention equipment and materials, endovascular embolization has become the primary choice, or important adjunct, in clinical treatment of vascular pathology. Coils and liquid embolic systems are the two most popular embolic materials. A problem with coils is the incomplete initial occlusion (<50% of vascular cavities) and the consequent recanalization due to the inherent physical constraints of coil therapy. There are limited liquid embolizing agents available for clinical use. Toxicity and lack of control are the main drawbacks. For example, the most used embolizing agent, Onyx, is composed of ethylene vinyl alcohol (EVAL) copolymer dissolved in dimethyl sulfoxide (DMSO). To obliterate the abnormal vasculature, Onyx is injected through a guided micro catheter, and its main component, EVAL, immediately precipitates and solidifies upon the diffusion of DMSO, which is known to be toxic in liquid form. The quick gelation may result in adherence of the microcatheter to the embolic mass; thus, the procedure must be carefully conducted by experienced radiologists and vascular surgeons. Moreover, Onyx is nonadhesive to vessel walls, which brings high risk of gel migration during and after operation. The side effects, difficult manipulation and potential complication lead to increased healthcare cost and unsatisfactory outcome.
A potential drawback of forming chemically crosslinked in situ hydrogels in some applications is the brittleness of the gel. Hydrogels formed by chemical crosslinking alone can be brittle and easily broken down into pieces at relatively small stress and small deformation. For many applications where the hydrogel is expected to experience forces such as, for example, in endoluminal therapy and tissue augmentation, where forces always exist, or for drug delivery and cell delivery, where forces may possibly exist, the ability of gels to be able to withstand a large stress or large extent of deformation is desirable.